The HORNBILL study: A Phase I/IIa trial examining the safety of BI-X in patients with diabetic macular ischemia and diabetic retinopathy treated with pan-retinal photocoagulation

Abstract

Purpose : Diabetic macular ischemia (DMI) is a vision-threatening and common complication of diabetic retinopathy (DR) that can lead to irreversible vision loss. At present, there is no approved treatment to prevent either the onset or progression of DMI. We are conducting a non-randomized, open-label, single rising dose/multiple rising dose study (NCT04424290) to investigate the safety and tolerability of intravitreal BI-X, an ischemia modulator agent.

Methods : Patients with DR treated with pan-retinal photocoagulation and evidence of DMI are eligible for inclusion. DMI was defined as any degree of disruption in retinal vascularity within the superficial and/or deep retinal plexus, imaged with optical coherence tomography angiography. A total of 6 patients have been enrolled into two dosing cohorts (0.5 mg and 1.0 mg of BI-X, n=3 per cohort) to date, with a future cohort at 2.5 mg (n=6) planned. Patients received a single intravitreal dose of BI-X. The primary endpoint is the number of dose-limiting events, with secondary endpoints being the number of drug-related adverse events (AEs) and number of ocular AEs.

Results : The mean age of the 6 patients was 62.8 (standard deviation ±10.7) years, 4 were female. No drug-related AEs or dose-limiting events were reported in either cohort, but 2 procedure related AEs were reported in the 0.5 mg cohort. One patient with glaucoma experienced a temporary increase in intraocular pressure (IOP), from 19 mmHg at baseline to 44 mmHg after injection. The patient was treated with topical anti-glaucoma therapies, after which IOP reduced to 35 mmHg; the patient reported no pain or discomfort. At follow up visits on days 4 and 8, IOP was 27 mmHg and 22 mmHg, respectively. A second patient had a subconjunctival hemorrhage that resolved without sequelae.

Conclusions : Single doses of BI-X were well-tolerated by patients with DMI, with no dose-limiting events, no SAEs and no drug related AEs reported to date. A single-masked, randomized, multiple rising dose study is planned to further examine the efficacy of BI-X in patients with DMI.

This is a 2021 ARVO Annual Meeting abstract.